Project Abstract: The development of new methods for the efficient and stereoselective preparation of amine-containing chemical building blocks is a compelling objective in organic synthesis as a large number of biologically active compounds contain an amino group bound to a stereogenic carbon. The chemical functionality that may flank the amine in these compounds is vast, including a number of commonly-encountered motifs, such as amino alcohols and diamines; additionally, the amine-bearing stereogenic center may be tri- or tetrasubstituted. Despite their frequency in targets of biological importance, methods for the stereoselective synthesis of 1,3- diamines, 1,3-amino alcohols, and amino-containing tetrasubstituted stereogenic centers are sparse, with the mode of their generation often labor intensive and/or circuitous. Several scaffolds within these frameworks have only rarely been produced. The long-term goal of this research program is to design and develop novel stereoselective C?C bond-forming methods for preparing difficult-to-access but highly sought-after chiral amines. Our strategy employs a polarity reversal of an imine (umpolung): rather than act as an N-substituted carbon electrophile, we transform the reagent to an N-substituted carbon nucleophile?a 2-azaallyl anion? that may be combined stereoselectively with a number of electrophilic partners to furnish alpha-substituted chiral amines. In these investigations, we will focus on C?C bond formations with 2-azaallyl anions for: 1) the stereoselective synthesis of challenging 1,3-diamine and amino alcohol functionality, 2) the enantioselective preparation of homoallylic amines with N-containing tetrasubstituted stereogenic centers, and 3) stereoselective three component coupling reactions with a silyl-substituted 2-azaallyl anion as a double alpha- amino anion equivalent. The new methods developed under the aegis of this project provide innovative solutions to long-standing challenges in the preparation of chiral amines that will permit streamlined synthesis of several biologically important complex molecules. The new chemical space that will be garnered might enable exploration of novel medicinal leads that may lead to active pharmaceutical ingredients to improve human health.